Individual Participant Data Network Meta-Analysis of Neoadjuvant Chemotherapy or Chemoradiotherapy in Esophageal or Gastroesophageal Junction Carcinoma
Authors: Matthieu Faron, Maurice Cheugoua-Zanetsie, Jayne Tierney, Pierre Thirion, Matthew Nankivell, Kathryn Winter, Hong Yang, Joel Shapiro, Dewi Vernerey, B. Mark Smithers, Thomas Walsh, Guillaume Piessen, Magnus Nilsson, Jurjen Boonstra, Marc Ychou, Simon Law, David Cunningham, Florent de Vathaire, Michael Stahl, Susan Urba, Michele Valmasoni, Danièle Williaume, Janine Thomas, Florian Lordick, Joel Tepper, Jack Roth, Val Gebski, Bryan Burmeister, Xavier Paoletti, Johanna van Sandick, Jianhua Fu, Jean-Pierre Pignon, Michel Ducreux, Stefan Michiels, Chanvitan Apinop, Anne Arezina, Emilie Barbier, Gary Bass, Pierre Blanchard, Jurjen Boonstra, Jean-François Bosset, Bryan H. Burmeister, Armel Maurice Cheugoua-Zanetsie, David Cunningham, Michel Ducreux, Matthieu Faron, Jianhua Fu, Val Gebski, D. J. Girling, David Kelsen, Fredrik Klevebro, Simon Law, Elisabeth Le Prise, Florian Lordick, Tanaphon Maipang, Murielle Mauer, Stefan Michiels, Jennifer Moughan, Matthew Nankivell, Knut Nygaard, Patrick Owens, Xavier Paoletti, Guillaume Piessen, Jean Pierre Pignon, Jean-Luc Raoul, Jack Roth, Alberto Ruol, Peter Schlag, Christoph Schumacher, Joel Shapiro, B. Mark Smithers, Michael Stahl, Joel Tepper, Pierre Thirion, Janine M. Thomas, Jayne Tierney, Susan Urba, Michele Valmasoni, Ate van der Gaast, Johanna van Sandick, Danièle Williaume, Kathryn Winter, John Wong, Hong Yang, Marc Ychou
Journal: Journal of Clinical Oncology (2023)

PURPOSE The optimal neoadjuvant treatment for resectable carcinoma of the thoracic esophagus (TE) or gastroesophageal junction (GEJ) remains a matter of debate. We performed an individual participant data (IPD) network meta-analysis (NMA) of randomized controlled trials (RCTs) to study the effect of chemotherapy or chemoradiotherapy, with a focus on tumor location and histology subgroups. PATIENTS AND METHODS All, published or unpublished, RCTs closed to accrual before December 31, 2015 and having compared at least two of the following strategies were eligible: upfront surgery (S), chemotherapy followed by surgery (CS), and chemoradiotherapy followed by surgery (CRS). All analyses were conducted on IPD obtained from investigators. The primary end point was overall survival (OS). The IPD-NMA was analyzed by a one-step mixed-effect Cox model adjusted for age, sex, tumor location, and histology. The NMA was registered in PROSPERO (CRD42018107158). RESULTS IPD were obtained for 26 of 35 RCTs (4,985 of 5,807 patients) corresponding to 12 comparisons for CS-S, 12 for CRS-S, and four for CRS-CS. CS and CRS led to increased OS when compared with S with hazard ratio (HR) = 0.86 (0.75 to 0.99), P = .03 and HR = 0.77 (0.68 to 0.87), P &lt; .001 respectively. The NMA comparison of CRS versus CS for OS gave a HR of 0.90 (0.74 to 1.09), P = .27 (consistency P = .26, heterogeneity P = .0038). For CS versus S, a larger effect on OS was observed for GEJ versus TE tumors ( P = .036). For the CRS versus S and CRS versus CS, a larger effect on OS was observed for women ( P = .003, .012, respectively). CONCLUSION Neoadjuvant chemotherapy and chemoradiotherapy were consistently better than S alone across histology, but with some variation in the magnitude of treatment effect by sex for CRS and tumor location for CS. A strong OS difference between CS and CRS was not identified.